Zona pellucida (ZP) antigens are potential candidates for contraceptive vaccines. However, specific antigenic domains associated with ZP molecules must be evaluated for efficacy in fertilization inhibition as well as for potential interference with normal ovarian function. Recent advances in molecular cloning of cDNA's for ZP antigens have rapidly facilitated our ability to dissect antigenic domains associated with the ZP of different mammalian species. Our recent macaque studies have demonstrated that ZP proteins expressed using recombinant cDNA technology can be used to generate antibodies which recognize native ZP proteins. These studies have demonstrated that a) two bacterially expressed rabbit ZP proteins will elicit an immune response; b) one of these prtoteins (Rec 55) produced antibodies which inhibit macaque sperm from binding to macaque ZP in vitro; and c) a year of sustained titers had no adverse effects on ovarian function or morphology in the Rec55 group. We have finished trials with female cynomolgus macaques which were immunized with Rec55 and BV-Rec55. BV-Rec55 is produced in the baculovirus expression system in eukaryotic cells to produce glycosylated recombinant proteins which may enhance the immunogenicity of the protein. All of the macaques responsed to the BV-Rec55 protein with increased serum titers, however these high serum titers did not provide a contraceptive effect during mating trials. The females immunized with Rec55 did not develop significant serum titers. Two females did have low to moderate serum anti-Rec55 titers, and serum from these animals will be used to test effects of the antibodies on sperm-zona binding, zona-induced acrosome reactions and zona penetration. The ovaries from the 2 animals with low to moderate titers were normally functioning and contained normal numbers of developing follicles. Zonae recovered from these ovaries will be utilized in sperm-zona interaction studies in vitro. *KEY* Contraceptive vaccine, Macaques